Bioidentical Hormones - U.S. Senate Special Committee on Aging

181
2 fl Postmenopausal hormone therapy
and cardiovascular disease
Jacques E Rossouw
Gender and cardlovascular disease
In the United States the number of women who die annually
from cardiovascular disease Is higher than men. The
cardiovascular disease burden Is particularly high in older
women. In women aged 55 and older, major cardiovascular
diseases (ICD 390-448-9) accounted for 473569 deaths In
1997 compared to 402310 deaths in older men.' Major cardiovascular
diseases accounted for 44% of all deaths in older
women and 40% of all deaths in older men. The number of
deaths from coronary heart disease (CHD) was only slightly
higher In older women (229628) tham In men (223246), but
the number of deaths from stroke was considerably higher
in women (88 768 compared to SS 149 respectively). There
were 4607 deaths from pulmonary embolism in older women
compared to 3465 In men. As exempllfied by these absolute
numbers of deaths, cardiovascular disease now represents
a larger health problem in older women than in older men.
CHD in particular occurs at a later age in women than In
men, and this is one reason why early trials (Incduding estrogen
trals) attempting to prevent premature' CHD focused
on middle-aged men. On average, death from CHD occurs
about lo years laterin women (Rgure20.1( than in men. The
2 -, J._
Coromry
uo lmnWar y
embolism
35-44 45-54 as-64 es-74 7-844 5-
Age
Figure 20.1 Annual mortality rates by t0 year age groups for
CHD, stroke, and pulmonary embolism in US women, 197.'
Inset Comparison of coronary heart disease mortality rates by
age for men and wrnen
incidence rate of CHD mortality rises after the age of 65, and
rises particularly steeply after 75 years when the great majortry
of CHD events occur Though their Incidence rates remain
lower at any age than In men, the fact that older women with
CHD outnumber men explaIns why the absolute number of
CHD deaths is higher in women. Deaths from strokes and pulmonary
embolism also rise markedly with age. Since CHD
and strokes are the major contributors to overall cardiovascular
disease rates, the effects of estrogen on these conditions
will dominate the overall cardiovascular outcome.
The sex differential in the age of onset of CHD is also one
of the reasons why estrogen is of interest as a potential preventive
treatment for CHD. Upid levels In children of both
sexes are similar until puberty, when high density Upoprotein
(HDL) cholesterol levels fall by about IO mg/di in boys
only, while low density Upoprotein (LDL) cholesterol levels
decrease by about 5 mg/dl In girls. 2 These changes may be
attributable to rising androgen and estrogen levels in boys
and girls respectively. The sex differential for HDL cholesterol
persists through adult life, but is less masked in older
persons. LDL cholesterol levels rise during adulthood,
and in older women LDL cholesterol levels eventually
catch up with those In men. Estrogen levels In women gradually
dednie, siarlug some years before the menopause,
during which time LDL cholesterol levels rise and HDL cholesterol
levels decrease. These lpid changes may underlie
the lower CHD risk In premenopausal women, and the
gradual Increase In postmenopausal women. However, the
menopause does not represent a sharp demarcation In risk;
some longitudinal studies have not shown changes in risk
factors over the menopause, and the rise in coronary rates
may simply reflect the effects of aging itself, as suggested
when the data for coronary deaths are plotted on a semllogsrithmic
scale (Figure 2O.2).1 Nonetheless, premature
menopause due to Dophorectomy Is associated with a higher
CHD rtisk, and oophorectomy followed by estrogen therapy
is not associated with Increased risk for CHD. 5 When exogenous
estrogen Is administered via the oral route to postmenopausal
women, LDL cholesterol levels decrease, HDL
cholesterol levels Increase, triglyceride levels Increase, and
1ipoproteln (a) levels decrease.6' 0 However, exogenous oral
estrogen has multiple non-Lpid effects. Some changes in
coagulation factors are potentially favorable (for example,